Review
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Transplant. Jun 18, 2025; 15(2): 99952
Published online Jun 18, 2025. doi: 10.5500/wjt.v15.i2.99952
Donor-specific antibodies against HLA-C, HLA-DP and HLA-DQ and their implications in kidney transplantation
Muhammad Abdul Mabood Khalil, Nihal Mohammed Sadagah, Ishida Hediki, Jackson Tan, Salem H Al-Qurashi
Muhammad Abdul Mabood Khalil, Nihal Mohammed Sadagah, Salem H Al-Qurashi, Center of Renal Diseases and Transplantation, King Fahad Armed Forces Hospital Jeddah, Jeddah 23311, Saudi Arabia
Ishida Hediki, Department of Urology and Transplantation, Tokyo Women's Medical University Hospital, Tokyo 162-8666, Japan
Jackson Tan, Department of Nephrology, RIPAS Hospital Brunei Darussalam, Brunei Muara BA1710, Brunei Darussalam
Author contributions: Khalil MAM and Al-Qurashi SH were responsible for the idea; all authors contributed to literature search, the intellectual content conception, writing the manuscript, and design of this study; all the authors read and agreed with the content of the manuscript.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Muhammad Abdul Mabood Khalil, FCPS, FRCP, Doctor, Center of Renal Diseases and Transplantation, King Fahad Armed Forces Hospital Jeddah, Al Kurnaysh Br Road, Al Andalus, Jeddah 23311, Saudi Arabia. doctorkhalil1975@hotmail.com
Received: August 3, 2024
Revised: October 11, 2024
Accepted: December 3, 2024
Published online: June 18, 2025
Processing time: 201 Days and 16.7 Hours
Abstract

HLA-C, HLA-DP and HLA-DQ are thought to be benign due to low expression and few initial negative studies. Historically, most allocation programs used HLA-A, HLA-B and HLA-DR antigens for matching. With the advent and use of single-bead antigen assays, more was learned about donor-specific antibodies (DSAs) against these antigens. Interest in these antigens and antibodies grew when cases of acute antibody-mediated rejection (AMR), mixed rejections, chronic AMR, and reduced graft survival were reported with DSAs against these antigens. Although the deleterious effects of these DSAs are more pronounced in retransplants, harmful effects have also been observed in first-time recipients. DSAs against each of these antigens can trigger rejection alone. Their combination with DSAs against HLA-A, HLA-B and HLA-DR can cause more damage. It has been shown that strategies that reduce mismatches for these antigen lead to fewer rejections and better graft survival. There is a need for greater consensus on the universal typing of these antigens prior to transplantation for better patient and graft outcomes. This review focuses on the interaction of these antigens with lymphocytes and killer immunoglobulin receptors, arguments for not typing them, detailed analyses of the literature about their harmful effects, potential strategies moving forward, and recommendations for the future.

Keywords: Kidney transplantation; HLA-C; HLA-DP; HLA-DQ; Donor specific antibodies; Review

Core Tip: HLA-C, HLA-DP and HLA-DQ are capable of initiating alloimmune responses and donor-specific antibodies (DSAs), which can cause antibody-mediated rejection (AMR), mixed rejection, chronic AMR and reduced graft survival. Better matching for these antigens could reduce production of DSAs, leading to better graft and patient outcomes. This review explores the reasons for not typing these antigens in the past, examines evidence for their harmful effects, and proposes a way forward that will help clinicians to avoid or minimize the harmful effects of these DSAs.